The goal of the laboratory is to understand the cell biology of epidermal Langerhans cells (LC); especially those aspects that explain special properties of LC such as their susceptibility to functional inactivation by ultraviolet (UV) radiation, their ability to initiate primary immune responses and their propensity to localize in the epidermis. We have demonstrated that doses of UVB that functionally inactivate LC prevent enhanced expression of ICAM-1 (CD54), and that interaction of ICAM-1 on LC with LFA-1 on T cells is prerequisite for LC-T cell cluster formation and anti-CD3 mAb-induced T cell proliferation. We have also observed that cultured LC (that express high levels of ICAM-1 and perhaps other adhesion molecules) are resistant to doses of UVB that inactivate fresh LC. These studies are confounded by subsequent studies that showed that doses of UVB radiation that modulate ICAM-1 expression and LC accessory cell activity were ultimately cytotoxic for LC. Similar cytotoxic effects of UV for LC were noted with biologically active amounts of UVC and psoralen + UVA radiation in vitro, and may be responsible for certain immunosuppressive effects of low dose UV radiation in vivo. Studies designed to identify additional important adhesion (or costimulatory) molecules on LC are ongoing. mRNA encoding the murine homologue of the B cell activation antigen B7 (BB1), a costimulatory molecule thought to be important in the activation of Th1 cells, has been reverse transcribed, amplified using the polymerase chain reaction and detected in samples of epidermal cell RNA by autoradiography, after fluid-phase hybridization with complementary radiolabelled synthetic oligonucleotides. Quantitative studies have revealed that cultured LC express 100-1000x more B7 mRNA than fresh LC or keratinocytes (KC) and 10-100x more B7 mRNA than the reference cell line CH-1. Cultured murine LC also provide costimulatory activity for human T cells in a xenogeneic assay that we believe measures B7 functional activity. Expression of B7 by cultured LC may be largely responsible for the ability of LC to activate unprimed LC. Very recent studies may also provide insight into mechanisms that promote the localization of LC in epidermis. We have determined that LC express cadherins, that LC adhere to E-cadherin expressing cells in vitro, and that anti-E-cadherin mAb abrogates LC-KC binding. E-cadherin expression by LC reflects endogenous synthesis since LC also contain E-cadherin mRNA. The role that cadherins play in LC biology and in the localization of other leukocytes in epithelia is under investigation.